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2 This Annual Report presents the scientific output from the Aging Research Center and the Stockholm Gerontology Research Center during the year These two multidisciplinary research centers are co-located in the House of Aging Research within the Sabbatsberg area in Stockholm, Sweden. The Aging Research Center is an academic institution within the Division of Geriatric Epidemiology (DOGE), Neurotec, Karolinska Institutet and the University of Stockholm (KI-SU-ARC), whereas the Stockholm Gerontology Research Center receives its funding from the Stockholm County Council and the City of Stockholm and has a strong commitment toward applied issues in aging and the dissemination of relevant knowledge to practitioners. In addition, research from three other units within DOGE, the Sophiahemmet Research Group, the Center for Gerontology and Health Economics, and the Unit for International Aging Research, is represented in the report. In this way, the Annual Report involves a combination of theoretically and practically oriented work on aging. We are happy to note that the year 2002 has been very productive in terms of publications. The report contains abstracts of 73 articles published in peer-reviewed journals, 24 chapters in edited volumes, 6 edited books, and 18 institutional reports. The report further indicates the substantial breadth of the gerontological and geriatric research carried out in the house, ranging from brain imaging and pharmacology through epidemiology and cognitive psychology to sociology and social work. It is hoped that the Annual Report will provide an accessible and informative picture of our research, and assist in creating communicative channels among researchers as well as between researchers and society at large. 2

3 Agüero-Torres H, Qiu C, Winblad B, Fratiglioni L. Dementing disorders in the elderly: Evolution of disease severity over seven years. Alzheimer Disease and Associated Disorders in press. ABSTRACT: The goal of this study was to describe the evolution of dementia severity in a very old dementia population. We investigated a representative group of demented subjects gathered from a population-based study (n=223). Changes in cognition, functioning, and performance on global scales were followed over a period of seven years. At baseline, 19% of the demented subjects were found to be severely impaired according to the Clinical Dementia Rating scale (CDR), 41% according to the Mini-Mental State Examination score (MMSE), and 31% according to Katz activities of daily living scale (ADL). After seven years, these proportions were 78%, 93%, and 68%, respectively. The probability of surviving three years, five years, and seven years after baseline examination was 48%, 28%, and 15%, respectively. Over a seven-year follow-up period, subjects suffering from questionable-mild dementia had a mean survival of 3.9 years (95% CI=3.3 to 4.5), while subjects with severe dementia survived on average 2.9 years (95% CI=2.5 to 3.2). Male gender, lower education, and poor cognitive and functional status were associated with shorter survival in milder cases, while the only factors that predicted shorter survival in more severe cases were older age and poor functional status. Long-term survivors in dementia are not rare, and as the absolute number of demented people is increasing, expanding our knowledge of these persons is of high public health importance. Key words: dementia, natural history, CDR, ADL, MMSE Agüero-Torres H, Thomas VS, Winblad B, Fratiglioni L. The impact of somatic and cognitive disorders on the functional status of the elderly. J Clin Epidemiol in press. ABSTRACT: To estimate the relative effects of co-existing non-dementia illnesses on the probability of functional disability, depending on the presence of cognitive impairment or dementia, we used data from the baseline case-control assessment of a longitudinal study of aging and dementia. Our study included 668 subjects (345 non-demented, 98 cognitively impaired, and 225 demented), aged 75 and older. Demented subjects had greater disability prevalence on all specific IADL and ADL items than cognitively impaired subjects who in turn had greater disability than non-demented subjects. Somatic illnesses were found to be associated with particular tasks in item specific models; decreasing MMSE was strongly associated with the probability of IADL and ADL disability, which increased dramatically in the presence of somatic illnesses among cognitively impaired as well as demented subjects. Attention to illnesses among cognitively impaired and demented people may shed light on remediable factors crucial to their daily functioning. Key words: functional status, somatic disorders, cognitive function, elderly Andersson L, Minell M. Om synen på våra gamla och åldrandet. Socialmedicinsk tidskrift 2002; 79: Artikeln handlar om uppkomsten av begreppet ageism/ålderism och hur detta beskrivits sedan slutet av 1960-talet. Därefter behandlas frågan om äldre generationer blir sämre bemötta i samhället än yngre generationer. Artikeln avslutas med en kort sammanfattning av 3

6 social network, substance use) on rate of cognitive change from preclinical to clinical AD. Using data from a population-based study, 230 persons who were non-demented at baseline and diagnosed with AD at a three-year follow-up were examined with the Mini-Mental State Examination (MMSE). Of all predictor variables examined, only number of diseases resulting in hospital admission during the follow-up period made an independent contribution to rate of MMSE change. These results suggest that many variables affecting the onset of the degenerative process as well as cognitive functioning in normal aging exert little influence on rate of cognitive change in preclinical AD. This may reflect the fact that the emerging dementia disease overshadows the role of these variables for cognitive functioning. A possible exception to this pattern is that an increasing number of concomitant health conditions may exacerbate rate of cognitive decline during the final portion of the preclinical phase in AD. Key words: Alzheimer s disease, preclinical, global cognitive ability, rate of change, predictors, comorbidity Bäckman L, Jonsson E, Wahlin Å, Small BJ, Fratiglioni L. Influences of preclinical dementia and impending death on the magnitude of age-related cognitive deficits. Psychol Aging 2002; 17: Using data from a subsample (n = 337) within a population-based study of persons between 75 and 96 years of age, we examined the influence of preclinical dementia (n = 61) and impending death (n = 69) on the cross-sectional relationship between age and performance in tasks assessing episodic memory (recall of random and organizable words, word and face recognition), visuospatial ability (Block Design and Clock Setting), and verbal fluency (category and letter fluency). Increasing age was associated with a general decrease in cognitive performance. In addition, those who were to be diagnosed with dementia or had died by a 3-year follow-up were older and performed at a lower level than the remaining sample across all cognitive tasks at baseline. Nevertheless, removal of the preclinical dementia and impending death groups from the original sample affected relatively little the cross-sectional age-cognition relations. This pattern of findings suggests that the biological aging process exerts negative influences on cognitive functioning beyond those resulting from disease and mortality. Key words: Alzheimer s disease, dementia, preclinical, terminal decline episodic memory, verbal fluency, visuospatial skill Bäckman L, Small BJ, Fratiglioni L. Cognitive deficits in preclinical Alzheimer s disease: Current knowledge and future directions. In: Dixon RA, Bäckman L, Nilsson LG, eds. New frontiers in cognitive aging. New York: Oxford University Press; in press. A robust impairment of episodic memory is seen in the preclinical phase of Alzheimer s disease (AD). This pattern is consistent with evidence from histopathological and brain imaging studies that the medial-temporal lobe is affected in the preclinical phase of AD. The vital importance of this brain region for successful episodic memory functioning is well documented in both lesion and brain imaging research. Recent research suggests that the size of the memory impairment in preclinical AD is quite stable up until the time period just preceding diagnosis, although these persons may show deficits several decades before diagnosis. These phenomena may reflect the facts that those biological events that eventually 6

7 lead to clinically diagnosed AD progress at a very slow rate, and that the aging brain can counteract these alterations until a certain threshold is reached beyond which compensatory processes no longer can withstand the accumulation of neural changes. The identification of persons during the transition from normal aging to AD may be enhanced by combining objective cognitive markers with other indicators, including subjective reports, biological markers, as well as precipitating factors. Importantly, provided that the level of cognitive impairment among those who will develop AD remains relatively stable for a long period until the dramatic decline seen in the last years before diagnosis, there is a large time window during which different types of intervention should be possible. Key words: Alzheimer s disease, preclinical, markers, episodic memory, compensation Bäckman L, Small BJ, Fratiglioni L. The nature and course of the memory impairment in Alzheimer s disease: From the preclinical phase to early clinical manifestations. In: Graf P, Ohta N, eds. Life-span development of human memory. Cambridge, MA: MIT Press; In this chapter, we discuss the cognitive consequences of Alzheimer s disease (AD), focusing largely on memory problems the cardinal symptom of the disease. In early clinical AD, there is evidence that primary memory, procedural memory, as well as various forms of priming are relatively little affected. Moderate dementia-related deficits early on in the pathogenesis are seen for tasks assessing semantic memory and working memory. However, the largest and most consistent impairment is observed in episodic memory tasks. However, contrary to previous assertions, AD patients are able to benefit from cognitive support (e.g., a rich stimulus input, instructions, cues) to improve episodic memory, although they need more support than the healthy aged to show memory facilitation. Several recent studies demonstrate that persons who will develop AD within a few years exhibit preclinical deficits in episodic memory tasks. Interestingly, a global deficit in episodic memory appears to precede reductions in cognitive reserve capacity in the early development of AD. A noteworthy observation is that measures of both free recall and recognition contribute to the identification of preclinical AD cases. Whereas free recall draws largely on conscious recollective operations, recognition involves a blend of conscious and unconscious processes. Thus, these findings suggest that both these classes of memory operations are affected several years prior to the actual AD diagnosis. Key words: Alzheimer s disease, cognitive support, preclinical, episodic memory, recall, recognition Bäckman L, von Hofsten C. Psychology at the millennium. Vol. 1: Cognitive, biological, and health perspectives. London: Psychology Press; This volume is based on keynote and state-of-the-art lectures within the areas of cognitive, biological, and health psychology from the 27 th International Congress of Psychology, held in Stockholm, Sweden, in July The volume is divided into five subsections. The first section deals with the neural mechanisms underlying psychological processes in humans and animals. The second part is devoted to the core areas in experimental psychology, perception, attention, learning, and memory. In the third section, chapters examine different aspects of psychological health, including stress, anxiety, and coping. The interaction between cognitive and emotional processes is the focus of the fourth part. Finally, in the fifth section, various types of higher cognitive processes are discussed (e.g., language, decision making). 7

8 Key words: cognitive psychology, biological psychology, health psychology Berger A-K, Fahlander K, Wahlin Å, Bäckman L. Negligible effects of depression on verbal and spatial performance in Alzheimer s disease. Dementia and Related Cogntive Disorders 2002; 13:1-7. ABSTRACT: We examined whether a diagnosis of depression affects verbal and visuospatial performance in Alzheimer s disease (AD). Using data from a population-based study, persons with AD and depression (AD/D), AD alone and a control group of normal older adults were compared in two tests of verbal ability (category and letter fluency) and two tests of visuospatial skill (block design and clock drawing). As expected, there were clear ADrelated deficits across all cognitive tasks. More importantly, the AD and AD/D groups were indistinguishable on all task variables. The lack of effects of depression was discussed relative to the view that those symptoms of this disease which are especially detrimental to cognitive functioning (e.g., concentration difficulties, lack of interest, loss of energy) may already be present in AD as a result of the neurodegenerative process. Key words: Alzheimer s disease, depression, comorbidity, verbal fluency, visuospatial skill Björkman IK, Fastbom J, Schmidt IK, Bernsten CB. the Pharmaceutical Care of the Elderly in Europe Research, (PEER) Group. Drug-drug interactions in the elderly. Annals of Pharmacotherapy 2002; 36: OBJECTIVE: To detect the frequency of potential drug-drug interactions (DDIs) in an outpatient group of elderly people in 6 European countries, as well as to describe differences among countries. DATA SOURCES AND METHODS: Drug use data were collected from 1601 elderly persons living in 6 European countries. The study population participated in a controlled intervention study over 18 months investigating the impact of pharmaceutical care. Potential DDIs were studied using a computerized detection program. RESULTS: The elderly population used on average 7.0 drugs per person; 46% had at least 1 drug combination possibly leading to a DDI. On average, there were 0.83 potential DDIs per person. Almost 10% of the potential DDIs were classified to be avoided according to the Swedish interaction classification system, but nearly one-third of them were to be avoided only for predisposed patients. The risk of subtherapeutic effect as a result of a potential DDI was as common as the risk of adverse reactions. Furthermore, we found differences in the frequency and type of potential DDIs among the countries. CONCLUSIONS: Potential DDIs are common in elderly people using many drugs and are part of a normal drug regimen. Some combinations are likely to have negative effects; more attention must be focused on detecting and monitoring patients using such combinations. As differences in potential DDIs among countries were found, the reasons for this variability need to be explored in further studies. Key words: aged, drug-drug interactions, pharmaceutical care, Europe De Frias CM, Dixon RA, Bäckman L. Use of memory compensation strategies is related to psychosocial and health indicators. J Gerontol Psychol Sci in press. Research has shown that psychosocial and health characteristics may affect older adults cognitive performance, self-referent beliefs, and general adaptive resilience. Are such 8

9 characteristics related specifically to older adults reported efforts to compensate for memory losses? The Memory Compensation Questionnaire (MCQ) measures five mechanisms of everyday memory compensation, as well as two general aspects of compensatory motivation and awareness. Correlates were derived from indicators of specific health conditions, subjective health ratings, personality, well being, and memory self-efficacy (MSE). All measures were administered to a cross-sectional sample of 528 healthy older adults between 55 and 94 years of age from the Victoria Longitudinal Study. Specific health composites (i.e., infirmities, respiratory illness), several personality dimensions (e.g., agreeableness, neuroticism), negative affect, and low MSE were associated with more frequent use of everyday memory compensation strategies. Linking healthy older adults cognitive resilience with individual characteristics is an important contribution to emerging conceptions of adaptation and success in late life. Key words: compensation, memory, questionnaire, aging, correlates, personality, selfefficacy, health, affect De Ronchi D, Faranca I, Borderi M, Manfredi R, Lunardi A, Fratiglioni L. Risk factors for cognitive impairment in HIV-1 infected persons with different risk behaviors. Arch Neurol 2002; 9: CONTEXT: Although it is well-established that AIDS dementia complex (ADC) mainly develops in patients with advanced HIV-1 infection and severe immunosuppression, other factors that might increase the risk of early neuropsychological abnormalities are controversial. OBJECTIVE: To identify risk factors of HIV-1-related cognitive impairment. DESIGN: Case-control study. SETTING: Division of Infectious Diseases, University of Bologna, Italy. PARTICIPANTS: 272 consecutive subjects, including 90 HIV-1- seronegatives, 88 asymptomatic HIV-1-seropositives, and 94 symptomatic HIV-1- seropositives. MAIN OUTCOME MEASURES: Cognitive impairment was defined as poor performance on at least two of the seven neuropsychological tests included in the battery. Cut-off scores for poor performance in a test were established as two or more standard deviations lower than the mean of the seronegative group in the corresponding risk behavior strata: injecting drug users (IDUs), hemophiliacs, and other risk behaviors. The following risk factors were studied: age, gender, education, risk behaviors, HIV-1 stage, lymphocyte count, and antiretroviral therapy. RESULTS: When compared with subjects with higher levels of education, subjects with less than six years of schooling had an odds ratio (OR) of 17.2 (95% C.I.= ) for cognitive impairment, independent of age, gender, disease stage, antiretroviral therapy, and risk behavior. When compared to IDUs, homo-bisexual and heterosexual subjects had an OR of 9.6 (95% C.I.= ), and 6.3 (95% C.I.= ) for cognitive impairment, respectively. The use of antiretroviral treatment (any versus none) was associated with lower prevalence of cognitive impairment (OR=0.1;95% C.I.= ). When compared with persons with high 0.50x109/L) CD4+ cell counts, subjects with low (<0.20x109/L) and moderate ( x109/L) CD4+ cell counts had an adjusted OR of 8.6 (95% C.I.= ), and 6.9 (95% C.I.= ), respectively. The presence of prominent depressive symptoms did not change the results. CONCLUSION: Low education, low CD4+ cell count, and homo-bisexual/heterosexual risk behaviors are risk factors for cognitive impairment in HIV-1-seropositive persons. The antiretroviral therapy exerts a beneficial effect against cognitive impairment in symptomatic subjects. Our findings suggest that homo-bisexual/heterosexual persons, who survive longer, are expected to be the group at 9

10 highest risk for cognitive impairment. However, the protective effect of antiretroviral therapy may balance this increased risk. Derwinger A, Stigsdotter Neely A, Persson M, Hill RD, Bäckman L. Remembering numbers in old age: Mnemonic training versus self-generated strategy training. Aging, Neuropsychology and Cognition in press. ABSTRACT: The effectiveness of two memory training programs designed to enhance 4 digit-number-recall was examined in 90 healthy older adults. One group received instruction and training in the number-consonant mnemonic, whereas another group was instructed to adopt their own encoding and retrieval strategies to enhance number recall. Also, a control group receiving no training between testing occasions was included. The criterion task was administered according to the Buschke selective reminding procedure. Posttest performance was evaluated with and without cognitive support for remembering (i.e., verbal cues). Under unsupported conditions, the mnemonic group improved number recall following training and the self-generated strategy group showed a tendency in the same direction. When support was provided, group differences in favor of the two training groups increased. In addition, no training-related gains were observed in two verbal transfer tasks. The relatively similar patterns of gains in the two intervention groups were discussed in terms of advantages and disadvantages in the two training regimens balancing each other. Key words: numerical memory training, self-generated versus tutor provided strategy Dixon RA, Bäckman L, Nilsson L-G. New frontiers in cognitive aging. New York: Oxford University Press; in press. This volume contains a collection of 17 chapters that all address novel approaches to the study of cognitive aging. The contributions are divided into three subsections. The first deals with new theoretical orientations in cognitive aging; the second addresses new directions in the cognitive neuroscience of aging; and the third is devoted to the influence of biological and health factors on cognitive aging. Each subsection is closed by integrative commentaries. Key words: cognition, aging, neuroscience, biological factors, health Dixon RA, Hopp G, Bäckman L. Memory compensation in normal aging and Alzheimer s disease. J Clin Exp Neuropsychol in press. Evidence pertaining to self-reported use of memory compensation techniques was collected using the Memory Compensation Questionnaire (MCQ). Five forms of everyday memory compensation were evaluated: (a) external memory aids, (b) internal mnemonic strategies, (c) investing and managing processing time, (d) applying more effort, and (e) reliance on human memory aids. The sample was derived from the Kungsholmen Project in Stockholm, Sweden, and consisted of 85 healthy older adults (M age= years; M MMSE score = 28.34) and 21 diagnosed Alzheimer s Disease (AD) patients (M age=81.80 years; M MMSE score = 23.55). Participants were tested on two occasions, six months apart. Results showed that the MCQ was a largely reliable instrument in these two groups. Moreover, we observed substantial sample similarity in frequency of using the five forms of everyday memory compensation techniques. The healthy sample reported using the external techniques more than the AD sample. Over the six-month interval, however, AD patients differentially 10

11 increased their use of others to assist them in everyday memory performance. Results are interpreted in terms of insight into changes in memory skills and in the implementation of effective memory support systems. Key words: compensation, memory, questionnaire, aging, Alzheimer s disease Dixon RA, Wahlin Å, Maitland SB, Hultsch DF, Hertzog C, Bäckman L. Episodic memory change in adulthood: Generalizability across samples and performance indices. Mem Cognit in press. Much cross-sectional research has confirmed that older adults recall substantially less information in episodic memory tasks than younger adults. Research focusing on actual changes in late-life performance, however, is relatively rare. We examine short-term change in a battery of episodic memory indicators (e.g., categorizable words, random words, prose passages) in two different longitudinal samples of older adults. Together, two-wave data both from the Victoria Longitudinal Study in Canada (VLS; n = 400) and the Kungsholmen Project in Sweden (KP; n = 168) cover a 40-year span of adulthood. Age groups include Young-old (VLS; years), Mid-old (VLS; years), Old-old (VLS and KP; years), and Very old (KP; years) adults each of which was tested twice, three years apart. Overall, examination of performance on sets of both similar and dissimilar episodic tasks revealed that for both samples actual 3-year changes are modest and that when decline occurs it is gradual. Discussion focuses on generalizability across episodic tasks, age groups, gender, and sample. Key words: episodic memory, word recall, prose recall, word recognition, aging, longitudinal, multiple indicators Fahlander K, Wahlin Å, Almkvist O, Bäckman L. Cognitive functioning in Alzheimer s disease and vascular dementia: Further evidence for similar patterns of deficits. Journal of Clinical and Experimental Neuropsychology 2002; 24: ABSTRACT: The purpose of the present study was to examine possible differences in patterns of cognitive performance between population-based samples of Alzheimer s disease (AD; n = 51) and vascular dementia (VaD; n = 14) patients between 75 and 96 years of age. The two demented groups were comparable in age, years of education, gender distribution, and severity of dementia. The selection of cognitive tasks (letter and category fluency, Block design, Clock reading and setting, and episodic face recognition) was thought to address some of the inconsistencies in previous research. The main finding was that AD and VaD patients were comparable on most tasks, although robust dementia-related deficiencies were found when comparing the results of the demented participants with those of the control participants. These findings suggest that AD and VaD may affect several basic cognitive functions in an equal manner. Key words: Alzheimers disease, major depression, comorbidity, cognition Fastbom J. Att ta medicin när man är äldre. Infomedica (http://www.infomedica.se/sjd_ramasp?categoryid=249). 11

12 Fischer H, Andersson JLR, Furmark T, Fredrikson M. Right-sided human prefrontal brain activation during fear conditioning acquisition. Emotion 2002; 2: ABSTRACT: This H 15 2 O positron emission tomography (PET) study reports on relative regional cerebral blood flow (rcbf) alterations during fear conditioning in humans. In the PET scanner subjects viewed a TV-screen with visual white noise or snake videotapes displayed alone, then with electric shocks, followed by final presentations of white noise and snakes. Autonomic nervous system responses confirmed fear conditioning only to snakes. To reveal neural activation during acquisition, while equating sensory stimulation, scans during snakes with shocks and white noise alone was contrasted against white noise with shocks and snakes alone. During acquisition, rcbf increased in the right medial frontal gyrus, supporting a role for the prefrontal cortex in fear conditioning to unmasked evolutionary fear relevant stimuli. Key words: affect, emotion; learning; working memory; encoding; positron emission tomography Fischer H, Wright CI, Whalen PJ, McInerney SC, Shin LM, Rauch SL. Brain habituation during repeated exposure to fearful and neutral faces: A functional MRI study. Brain Research Bulletin in press. ABSTRACT: Central nervous system habituation in humans was studied using functional magnetic resonance imaging and repeated presentations of single fearful and neutral faces. Habituation of blood-oxygenation-level-dependent signal during exposure to face stimuli, collapsed over fearful and neutral expressions, was evident in the right amygdala and hippocampus, as well as in the medial/inferior temporal cortex bilaterally. In the hippocampus significantly greater habituation was evident on the right as compared to the left side, which could reflect the visual nature of the stimuli. There were no time by expression interaction effects in these regions, suggesting similar neural attenuation rates to fearful and neutral face stimuli. These results indicate that brain regions involved in novelty detection and memory processing habituate at similar rates regardless of whether the face in focus displays an aversive emotional expression or not. Key words: amygdala, emotion, facial expressions, hippocampus, human, neuroimaging Forsell Y, Palmer K, Fratiglioni L. Psychiatric symptoms/syndromes in elderly persons with mild cognitive impairment. Data from a cross-sectional study. Acta Neurologica Scandinavica (suppl) in press. OBJECTIVE: This study examined the prevalence of psychiatric syndromes and symptoms in elderly persons with Mild Cognitive Impairment (MCI). METHODS: Data from a population-based study, the Kungsholmen Project, was used. All subjects with an MMSE score 23 and a comparable random of those 24 were selected for further examination. Physicians carefully examined the included persons and those affected with dementia were excluded. The rest were stratified into 14 groups according to age and level of education. The mean MMSE score was calculated for each group and those subjects with scores 1 SD below the age-education specific mean were classified as MCI. A structured psychiatric interview was performed and diagnoses of Depression, Anxiety and Psychosis were made according to 12

14 Key words: elderly immigrants, semi informal caregiving, social care, migration, integration policy, care policy Fratiglioni L, Herlitz A, Kivipelto M. Estrogen and Alzheimer's disease: Putative treatment and prevention. Dementia 2002; 3:6-9. It has been suggested that estrogen replacement therapy (ERT) may prevent or delay the onset of Alzheimer s disease. Estrogen has several biological effects in the brain and effects on brain functioning which might explain the possible protective effect of this hormone against cognitive decline and dementia. Including specific mechanisms that may relate estrogen to Alzheimer s disease pathology. This review summarizes current knowledge in the following major subtopics: (I) the effects of estrogen on cognitive functioning; (ii) the relation between lifelong estrogen exposure and cognitive performance; (iii) the association between hormone replacement therapy (HRT) and Alzheimer s disease risk; and (iv) the use of estrogen as treatment in Alzheimer s disease. Key words: estrogen, dementia, cognition, memory, Alzheimer's disease, treatment Furmark T, Tillfors M, Marteinsdottir I, Fischer H, Pissiota A, Fredrikson M. Common changes in cerebral blood flow in patients with social phobia reated with citalopram or cognitive-behavioral therapy. Archives of General Psychiatry 2002; 59: BACKGROUND: Neurofunctional changes underlying effective antianxiety treatments are incompletely characterized. This study explored the effects of citopram and cognitivebehavioral therapy on regional cerebral blood flow (rcbf) in social phobia. METHODS: By means of positron emission tomography and oxygen 15-labeled water, rcbf was assessed in 18 previously untreated patients with social phobia during an anxiogenic public speaking task. Patients were matched for sex, age, and phobia severity, based on social anxiety questionnaire data, and randomized to citopram medication, cognitive behavioral group therapy, or a waiting-list control group. Scans were repeated after nine-weeks of treatment or waiting time. Outcome was assessed by subjective and psychophysiological state anxiety measures and self-report questionnaires. Questions were administrated after 1 year. RESULTS: Symptoms improved significantly and roughly equally with citalopram and cognitive-behavioral treatment whereas waiting-list controls remained unchanged. Four patients in each treated group and 1 waiting-list patient were classified as responders. Within both treated groups, and in responders regardless of treatment approach, improvement was accompanied by a decreased rcbf-response to public speaking bilaterally in the amygdala, hippocampus and the periamygdaloid, rhinal, and parahippocampal cortices. Between-group comparisons confirmed that rcbf in these regions decreased significantly more in treated groups than controls, and in responders than nonresponders, particularly in the right hemisphere. The degree of amygdalar-limbic attenuation was was associated with clinical improvement a year later. CONCLUSIONS: Common sites of action for citopram and cognitive-behavioral treatment of social phobic anxiety were observed in the amygdala, hippocampus, and neighboring cortical areas, i.e. brain regions subserving bodily defense reactions to threat stimuli. 14

15 Garcia-Jimenez A, Cowburn RF, Ohm TG, Lasn H, Winblad B, Bogdanovic N, Fastbom J. Loss of stimulatory effect of guanosine triphosphate on [ 35 S]GTPgammaS binding correlates with Alzheimer's disease neurofibrillary pathology in entorhinal cortex and CA1 hippocampal subfield. Journal of Neuroscience Research 2002; 67: Heterotrimeric guanosine triphosphate (GTP)-binding proteins (G-proteins) couple many different cell surface receptor types to intracellular effector mechanisms. Uncoupling between receptors and G-proteins and between G-proteins and adenylyl cyclase (AC) and phospholipase C (PLC) has been described for Alzheimer's disease (AD) brain. However, there is little information on whether altered G-protein signaling in AD is just an end-stage phenomenon or is important for the progression of disease pathology. Here we used [(35)S]GTPgammaS autoradiography to study G-protein distribution in sections of entorhinal cortex and hippocampus from 23 cases staged for neurofibrillary changes and amyloid deposits according to Braak and Braak (Acta Neuropathol. [1991] 82: ). We also studied the effects of GTP, which has been found to increase [(35)S]GTPgammaS binding in an Mg(2+)-dependent manner. Results show that the ability of GTP (3 microm) to stimulate [(35)S]GTPgammaS binding declined significantly with staging for neurofibrillary changes in the entorhinal cortex (P < 0.05, ANOVA) and CA1 subfield of the hippocampus (P < 0.05, ANOVA). No significant changes were seen for [(35)S]GTPgammaS binding in the absence of GTP. Our results suggest a decrease in G-protein GTP hydrolysis, which correlates with the progression of AD neurofibrillary changes, in the regions most affected by this pathology. These alterations appear to occur prior to stages corresponding to clinical disease and could lead to an impaired regulation of several signaling systems in AD brain. Key words: Alzheimer s disease, G-proteins, guanosine triphosphate, autoradiography, neurofibrillary changes Garfield FB, Getsios D, Caro JJ, Wimo A, Winblad B. Assessment of health economics in Alzheimer s disease (AHEAD). Treatment with galantamine in Sweden. Pharmacoeconomics 2002; 20(9): BACKGROUND: Like other developed countries with aging populations, Sweden is expecting large increases in the prevalence of Alzheimer's disease and corresponding escalations in the cost of care for patients with this disease. Galantamine, a new acetylcholinesterase inhibitor and nicotinic modulator, has proved effective in managing patients with Alzheimer's disease in clinical trials. OBJECTIVE: To estimate the long-term health and economic impact of galantamine from the perspective of the public health payer in Sweden. DESIGN AND SETTING: The Assessment of Health Economics in Alzheimer's Disease (AHEAD) model compares galantamine treatment with no pharmacologic treatment. It consists of a module based on trial data followed by a projection module that uses the trial results to predict the time until patients require full-time care (FTC) or until their death. Forecasts were made for up to 10 years. The model was customised to Sweden by using Swedish resource use profiles obtained from the literature. RESULTS: Galantamine is predicted to reduce the time patients require FTC by almost 10%. Approximately 5.6 patients with mild-to-moderate disease would need to be treated to avoid one year of FTC. This would result in savings averaging Swedish kronas (SEK) [3131 euros (EUR)] per patient over 10 years (1998 values). To avoid one year of FTC, 3.9 patients with moderate disease would need to be treated, with savings averaging SEK (EUR 5594) per patient over 10.5 years. Sensitivity analyses of key parameters, such as proportion of patients 15

16 needing FTC treated in the community, cost of care in an institution, cost of FTC care in the community, the price of galantamine, and the discount rate, found savings with galantamine would occur under most circumstances. CONCLUSION: Galantamine can increase the time before patients require FTC, and may also lead to savings as treatment costs are offset by reductions in other healthcare expenditures and the costs associated with FTC. Key words: Alzheimer s Disease, galantamine, full time care, costs, Sweden Giron MS, Forsell Y, Bernsten C, Thorslund M, Winblad B, Fastbom J. Sleep problems in a very old population: drug use and clinical correlates. Journal of Gerontology 2002;57:M BACKGROUND: Complaints of disturbed or dissatisfied sleep are common among older people. This study aimed to evaluate the prevalence of sleep problems in very old persons and its relation to physical and mental health and drug use. METHODS: This is a crosssectional analysis of sleep problems in a population of old persons living in Stockholm, Sweden. There were 641 subjects aged 81+ years; 77.8% were women, 91.4% were noninstitutionalized, and 68.6% lived alone. All persons underwent a comprehensive medical and psychiatric interview and examination. Sleep problems were assessed using the Clinical Psychopathological Rating Scale (CPRS). Covariates included chronic medical conditions, depression, dementia, pain, self-rated health, activities of daily living, use of hypnoticssedatives, use of other psychotropic drugs, and use of nonpsychotropic drugs. RESULTS: More than one third of subjects were identified with sleep problems. They were more common among women and persons using a higher number of drugs. Poor self-rated health, depression, and pain were related to the presence of sleep problems. Among persons with sleep problems and depression, only 19.2% used antidepressants, and 46.2% used hypnoticssedatives. Among persons with sleep problems and pain, 63.2% used analgesics, and 47.0% used hypnotics-sedatives. One or more chronic diseases, use of hypnotics-sedatives, use of other psychotropic drugs, and use of nonpsychotropic drugs were also related to sleep problems. After multivariate analysis, factors significantly related to sleep problems were female gender, depression, pain, and hypnotic-sedative use. CONCLUSIONS: Sleep problems were common in this very old population. These results suggest the importance of carefully assessing an older person's complaints to accurately diagnose and effectively treat sleep problems. Key words: aged, sleep, depression, pain, drug utilization, antidepressants, hypnoticssedatives Gurner U, Fastbom J. Vaxholm 1:an. Utvärdering av Turboprojektet i Vaxholm, 22 fallstudier av multisjuka 75+: Stiftelsen Stockholms Äldrecentrum; 2002:2. Äldrecentrum har, på uppdrag av Stockholms läns landsting, i flera studier visat att äldre med sammansatta behov inte garanteras en trygg och värdig vård och omsorg. Multisjuka/multisviktande äldre är högkonsumenter av vård och omsorg. Ansvaret för dem är splittrat mellan vård- och omsorgsnivåer samt mellan huvudmännen. De får omfattande insatser med bristfällig eller ingen sammantagen planering. Denna utvärdering har syftat till att studera hur primärvården i Vaxholm, med husläkarteam som bas, påverkat samarbetet mellan slutenvård, primärvård och äldreomsorg samt fungerat utifrån multisjuka äldres (75+) behov. Analyserna bygger på intervju-, register- och 16

18 groups were identified: those who survived the entire follow-up period (n = 40), those who died before the first follow-up (n = 44), and those who died after the first follow-up (n = 14). Participants completed a battery of episodic memory tasks consisting of face recognition, word recognition, word recall, and object recall with selective reminding. Those who survived performed better than those who were going to die in object recall at baseline. A Cox regression analysis, controlling age, revealed that object recall performance was significantly related to subsequent mortality status. Longitudinal analyses demonstrated significant 3-year decline for both face recognition and object recall, but no evidence of differential decline as a function of mortality group. Thus, longitudinal changes in memory preceding death were not as pronounced as the corresponding cross-sectional differences in this very old sample. In general, the results suggest that mortality-related memory deficits are present in extreme old age, although these deficits are relatively small and task-specific. Key words: terminal decline, episodic memory, mortality, word recall, object recall, word recognition, face recognition Herlitz A, Yonker J. Sex differences in episodic memory: The influence of IQ. Journal of Clinical and Experimental Neuropsychology 2002; 24: The influence of estimated intelligence (group assessment of WAIS-R S ) on sex differences in face recognition, as well as verbal and non-verbal episodic memory tasks was examined in 99 women and 88 men between 20 and 40 years of age. Results showed that men performed at a higher level than women on the WAIS-R S subtest Information, whereas the opposite was true for Digit symbol. Women performed at a higher level than men on the verbal episodic memory tasks and on face recognition, but there were no sex differences on the non-verbal episodic memory task. Estimated intelligence for both men and women was positively associated with most episodic memory measures, the exception being face recognition in women. In face recognition, there was no association to estimated intelligence, suggesting that face recognition performance in women is unrelated to several basic cognitive processes. Key words: sex differences, intelligence, IQ, episodic memory, face recognition Herlitz A, Yonker JE. Hormonal effects on cognition in adults. In: Dixon RA, Bäckman L, Nilsson L-G, eds. New frontiers in cognitive aging. Oxford: Oxford University Press; in press. In the search for biological influences on cognition, steroid hormones have proven to be engaging variables for over two decades. Hormones are claimed to affect a variety of cognitive abilities from spatial and verbal abilities to various forms of memory. Hormones and cognition have been compared both within and between men and women. The goal of this chapter is to present the rationale for studying sex hormones in relation to cognition and to discuss hormonal influences on cognitive functioning in adulthood and old age. We focus on the potential role of steroid hormones on sex differences in cognitive function across the adult life span. Testosterone, in particular, is examined for its possible influence on spatial abilities in both men and women. Additionally, we address questions regarding the effect on cognition of endogenous estrogen in pre- and postmenopausal women, the contribution of hormone replacement therapy (HRT) on cognition in postmenopausal women, and the potentially protective effect of estrogen for the development of Alzheimer s disease. Promising areas for future research are also highlighted. 18

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